U.S. flag

An official website of the United States government

NM_148919.4(PSMB8):c.815G>A (p.Arg272Gln) AND Proteasome-associated autoinflammatory syndrome 1

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 16, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000554127.8

Allele description [Variation Report for NM_148919.4(PSMB8):c.815G>A (p.Arg272Gln)]

NM_148919.4(PSMB8):c.815G>A (p.Arg272Gln)

Gene:
PSMB8:proteasome 20S subunit beta 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.32
Genomic location:
Preferred name:
NM_148919.4(PSMB8):c.815G>A (p.Arg272Gln)
HGVS:
  • NC_000006.12:g.32840975C>T
  • NG_009793.3:g.2796G>A
  • NG_028165.1:g.8961G>A
  • NM_004159.5:c.803G>A
  • NM_148919.4:c.815G>AMANE SELECT
  • NP_004150.1:p.Arg268Gln
  • NP_683720.2:p.Arg272Gln
  • LRG_1328t1:c.815G>A
  • LRG_1328t2:c.803G>A
  • LRG_1328:g.8961G>A
  • LRG_1328p1:p.Arg272Gln
  • LRG_1328p2:p.Arg268Gln
  • NC_000006.11:g.32808752C>T
  • NM_148919.3:c.815G>A
Protein change:
R268Q
Links:
dbSNP: rs368551668
NCBI 1000 Genomes Browser:
rs368551668
Molecular consequence:
  • NM_004159.5:c.803G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_148919.4:c.815G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Proteasome-associated autoinflammatory syndrome 1 (PRAAS1)
Synonyms:
Nakajo syndrome; Nodular erythema digital changes; JOINT CONTRACTURES, MUSCULAR ATROPHY, MICROCYTIC ANEMIA, AND PANNICULITIS-INDUCED LIPODYSTROPHY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0054698; MedGen: C4746851; Orphanet: 2615; Orphanet: 324977; Orphanet: 324999; Orphanet: 325004; OMIM: 256040

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000640474Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 16, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003920360Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Jul 12, 2022)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000640474.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 272 of the PSMB8 protein (p.Arg272Gln). This variant is present in population databases (rs368551668, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PSMB8-related conditions. ClinVar contains an entry for this variant (Variation ID: 465423). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV003920360.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.04% (18/41414) (https://gnomad.broadinstitute.org/variant/6-32840975-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:465423). This variant amino acid Glutamine (Gln) is present in several species including multiple mammals and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024